Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

H∞ control of switched linear discrete‐time systems with polytopic uncertainties

In this paper, the problem of designing H_∞ state‐feedback controllers for switched linear discrete‐time systems with polytopic uncertainties is investigated. Two approaches on designing robust and parameter‐dependent H_∞ controllers are proposed and the existence conditions of the desired controllers are derived and formulated in terms of a set of linear matrix inequalities. By solving the corresponding convex optimization problem, the desired controllers are obtained, respectively, and different optimal H_∞ noise‐attenuation level bounds of corresponding closed‐loop systems are given as well. The designed controllers have their own advantages and disadvantages regarding the conservatism and realization complexity. An illustrative example emerging in networked control systems (NCS) and numerical simulations are presented to show the applicability and effectiveness of the obtained theoretic results. Copyright © 2006 John Wiley & Sons, Ltd.     

A rare case of nasopharyngeal angiofibroma in an elderly female

Nasopharyngeal angiofibromas occur predominantly in males in their puberty and adolescence; the incidence in other age groups and in women is exceptional. This report describes a case of a 57-year-old woman with nasopharyngeal angiofibroma presenting typical radiological findings in computed tomography, MR imaging and angiography. The tumour was successfully removed and histopathological examination confirmed the diagnosis. In 6 years follow-up the patient is free of symptoms.     

Synthesis of furodiketochroman and bis-furocoumarin derivatives and their biological activity

A number of substituted furodiketochroman derivatives (III _a-f ) have been synthesized by fusion of aromatic aldehydes with 5-hydroxybergapten and 5-hydroxyisopimpinellin. On the other hand, when the reaction was carried out in a solvent, the corresponding bis-furocoumarin derivatives (IV _c-n ) were obtained. The anticoagulant effect of compoundsIII _a,b,d andIV _b,c,f,g,i,k , was tested. They failed to demonstrate any significant effect. The effect of the tested compounds on the arterial blood pressure was studied. CompoundsIV _c ,III _d ,III _b ,IV _b ,IV _g ,IV _k andIV _i showed lowering effects on the normal systolic blood pressure of anaesthetized rats in a decreasing manner.     

Some nucleophilic substitutions in 2,4-and 2,4,8-trichloro-pyrido [3,2-d] pyrimidines

Reaction of 6-(acetoxymethyl)-2,4-dichloropyrido[3,2-d]pyrimidine (I) with some nucleophiles was investigated. When I reacted with sodium azide afforded 2,4-diazido derivative (II). Treatment of II with sodium hydroxide underwent cyclization of the 2-azido group to tetrazolo, replacement of 4-azido group by hydroxide ion, and hydrolysis of 6-acetoxy moiety to hydroxy methyl derivative (III). While, reaction of I with hydrazine hydrate resulted in the formation of 2,4-dihydrozino-6-hydroxymethyl derivative (IV).     

Development of an enzyme‐linked immunosorbent assay (ELISA) for the detection of porcine pepsin as a milk clotting enzyme

An enzyme‐linked immunosorbent assay (ELISA) for the detection of porcine pepsin in milk‐clotting enzyme preparations has been developed. The assay is capable of detecting porcine pepsin in the range 1 μgto 1 mg ml^‐1 without enhancement or modification. The specificity of the technique was studied by inhibition assay. Slight cross‐reactions with bovine rennet and Mucor miehei rennet occurred at high concentrations (1.0 mg ml^‐1). The ELISA used in this investigation appears to provide a quick, sensitive and specific method for the detection of porcine pepsin and has potential applications in the dairy industry.     

Analysis of the four heart sounds statistical study and spectro-temporal characteristics

Abstract

Heart auscultation has been recognised for a long time as an important tool for the diagnosis of heart disease; it is the most common and widely recommended method to screen for structural abnormalities of the cardiovascular system. Detecting relevant characteristics and forming a diagnosis based on the sounds heard through a stethoscope, however, is a skill that can take years to be acquired and refine. The efficiency and accuracy of diagnosis based on heart sound auscultation can be improved considerably by using digital signal processing techniques to analyse phonocardiographic (PCG) signals. The study of the functioning of the heart is very important for the diagnosis of different cardiac pathologies. The phonocardiogram signal (PCG) is the signal generated after conversion of the sound noises coming from the heart into an electrical signal, it groups together a set of four cardiac noises (S1, S2, S3, S4) which are in direct correlation with cardiac activity. The short-term Fourier Transform (STFT) is an analytical technique that describes the evolution of the time and frequency behaviour of these four heart sounds. A statistical study has been carried out in this direction in order to better highlight the characteristics of the PCG signal. A fairly high number of cycles (twenty) was used to further refine the expected results. The objective of this paper is to use a statistical analysis based on the results obtained by the use of The STFT technic this in order to find statistical parameters (mean, standard deviation, etc.) which can give us a clear vision of the electrophysiological behaviour of the phonocardiogram signal. This aspect has not been done so far and which however can give appreciable practical results.     

Mechanotransduction of bone cells<Emphasis Type="Italic">in vitro</Emphasis>: Mechanobiology of bone tissue

Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the load profile and whether different components, such as fluid shear, tension or compression, can influence cells in differing ways. During dynamic loading of intact bone, fluid is pressed through the osteocyte canaliculi, and it has been demonstrated that fluid shear stress stimulates osteocytes to produce signalling molecules. It is less clear how mechanical loads act on mature osteoblasts present on the surface of cancellous or trabecular bone. Although tissue strain and fluid shear stress both cause cell deformation, these stimuli could excite different signalling pathways. This is confirmed by our experimental findings, in human bone cells, that strain applied through the substrate and fluid flow stimulate the release of signalling molecules to varying extents. Nitric oxide and prostaglandin E₂ values increased by between two- and nine-fold after treatment with pulsating fluid flow (0.6±0.3 Pa). Cyclic strain (1000 μstrain) stimulated the release of nitric oxide two-fold, but had no effect on prostaglandin E₂. Furthermore, substrate strains enhanced the bone matrix protein collagen I two-fold, whereas fluid shear caused a 50% reduction in collagen I. The relevance of these variations is discussed in relation to bone growth and remodelling. In applications such as tissue engineering, both stimuli offer possibilities for enhancing bone cell growth in vitro.     

Anti-HLA class I antibody-mediated activation of the PI3K/Akt signaling pathway and induction of Bcl-2 and Bcl-xL expression in endothelial cells

Anti-human leukocyte antigen (HLA) antibodies (Ab) have long been implicated in the process of acute and chronic allograft rejection, yet their mechanism(s) of action is not well understood. The aim of this study was to determine whether ligation of HLA class I molecules by anti-HLA Ab on the surface of human endothelial cells (EC) activates the PI3 Kinase (PI3K)/Akt signaling pathway and downstream target proteins of the cell death apparatus. We report that Ab ligation of major histocompatibility complex (MHC) class I molecules on the surface of EC triggers phosphorylation of Akt, PI3K, and recruitment of PI3K and Akt into a signaling unit with focal adhesion kinase. Signaling through class I also stimulated phosphorylation of Bad and upregulated expression of Bcl-2 and Bcl-xL. Pretreatment of EC with the PI3K inhibitor wortmannin blocked class I-mediated expression of Bcl-2, but not Bcl-xL, suggesting a role for the PI3K/Akt signaling pathway in regulation of class I-induced Bcl-2 expression. The intracellular events initiated by class I ligation were influenced by the concentration of the anti-HLA Ab with the lowest tested concentrations of Ab stimulating the highest level of Akt phosphorylation, Bcl-xL and Bcl-2 expression. Consistent with the in vitro experiments, analysis of biopsy samples from heart transplant recipients with evidence of Ab-mediated rejection exhibited increased Bcl-2 expression on the vascular endothelium. These results suggest that exposure of the graft endothelium to low concentrations of anti-HLA Ab may promote cell survival by transducing signals resulting in upregulation of cell survival genes.